For
thousands of years, human being has been using plants, herbs
and spices to survive and maintain good health. It is the
most natural, sensible and greatly beneficial way of life.
In the Asian tradition, the Chinese, Indian and Malays have
been using mixtures of herbs in herbal tea, drink, soup and
dishes

HEMPEDU BUMI or King of
Bitter, scientifically known as Andrographis paniculata

Description:

Hempedu Bumi is indigenous to South
East Asia. A decoction of its leaves is widely used for herbal
remedy to cure high blood pressure, diabetic, cancer and other
diseases. It is a 'wonder herbs' with a lot of potential.Hepatoprotective
and choleretic activityA. paniculata and its major constituent, andrographolide,
exhibited protective effects comparable to that of silymarin against
liver damage in rats induced by various hepatotoxic agents such as
carbon tetrachloride, t-butylhydroperoxide, galactosamine, and
paracetamol.(9,
10,
11,
12) In an in vitro study, andrographolide was
found to be superior and more potent than silymarin in reversing the
toxic effects of paracetamol on certain liver enzymes.(13)
Another study has shown that an alcohol extract of A. paniculata,
andrographolide, and neoandrographolide had a significant
anti-hepatotoxic effect against Plasmodium berghei
K173-induced hepatic damage of Mastomys natalensis.(14)
Andrographolide has shown choleretic activity in the rat and guinea
pig, increasing bile volume as well as the amount of bile salts and
bile acids.(15)
Other researchers have also reported the antioxidant and
hepatoprotective action of A. paniculata in t-butylhydroperoxide-induced
liver damage of mice.(16)`

Anti-diabetic propertiesA. paniculatawas also reported to have anti-diabetic
properties. A study reported that oral administration of the extract
significantly reduced the fasting serum glucose levels of diabetic
rats but not of normal rats when compared to metformin, a standard
anti-diabetic drug.(17)
Both andrographolide and A. paniculata extract accelerated
intestinal digestion and absorption of carbohydrates by activating
the brush border membrane bound hydrolases, e.g. lactase, maltase,
and sucrase of the small intestine.

Cardiovascular disorders
A crude aqueous extract of Andrographis paniculata as well as
its semi-purified fractions were found to produce a significant
dose-dependent fall in mean arterial blood pressure of rats.(19)
Another study has shown that the aqueous extract of A. paniculata
lowered systolic blood pressure by reducing circulating
angiotensin-converting enzyme in the plasma.(20)
Two of its diterpene lactones, 14-deoxyandrographolide and
14-deoxy-(11,12)-didehydroandrographolide (DDA), demonstrated
hypotensive effects in isolated rat aorta.(21)
DDA also significantly reduced mean arterial blood pressure and
heart rate of anaesthetized rats in a dose-dependent manner.(22)
Andrographolide inhibited PAF-induced human platelet aggregation in
a dose-dependent manner, thus supporting its anti-thrombotic
activity.(23)

Antipyretic and analgesic properties
In a study,(28)
andrographolide reduced the rectal body temperature at doses of 30,
100, and 300 mg per kg of bodyweight. The 300mg/kg dose of
andrographolide was as effective as the same amount of aspirin.
However, the analgesic activity of andrographolide was weak compared
to aspirin. In another study A. paniculata extracts were
found to produce results comparable to 200 mg of aspirin.

Andrographis paniculata (Burm.
F.) Nees is a herb from the family Acanthaceae,
found throughout Southeast Asia, and known
locally as "hempedu bumi" and "akar cerita".
This an annual herb has been commonly known as
'king of bitter' and is reported to have
analgesic, antimalarial, anti-inflammatory,
antineoplastic, antiulcerogenic, antibacterial,
febrifuge, antiplatelet, antidiarrhoeal and
antithrombotic properties, also possess
protective activity against various liver
disorders. It is a reputed remedy in Malaysia
for diabetes and hypertension (Ahmad & Asmawi,
1993; Int. Conf. On the Use of Traditional Med.
& Other Natural Products in Health Care, USM).

Some important chemical compounds were
been isolated from this plant. The aerial part contains
several diterpenoids and diterpene glycosides. Its main
constituent, andrographolide, a diterpene lactone, is mainly
responsible for its bitter taste. Besides, diterpene
lactones, flavone derivatives such as oroxylin and wogonin
were also isolated from the leaves. From its rhizomes,
several kinds of flavonoids and their glycosides
(andrographidine A-F) are found (Chan KL 2001).

Besides the diterpene andrographolide
compound, andrographiside and neoandrographolide have been
shown to have protective effects on hepatotoxicity induced
in mice by carbon tetrachloride or tert-butylhydroperoxide
(tBHP) (Kapil-A et al 1993; Biochem-Pharmacol., 46(1):
182-5).

A. paniculata is also traditionally known
to have antifertility effect. Studies done by giving
andrographolide (an active substance of A.paniculata) im
(intramuscular) to male rats (Jonarthanan S, 1990) and A.
paniculata dried leaves powder orally to male albino rats
(Akbarsha et.al, 1990) and female mice (Zoha et.al, 1989)
showed that A. paniculata has antifertility effect in male
as well and female subjects. However the possible mode of
action of the herb as contraceptive is yet to be determined.

On the other hand, Burgos et.al in 1997
failed to demonstrate any testicular toxicity caused by A.
paniculata dried extract in male Spraque Dawley rats. In
that study the animals were treated with dried ethanolic
extract of A. paniculata. Panossian et.al (1999) reported
that powder extract of A. paniculata leaves (Kan Jang
tablet: Andrographolide 4.6% and deoxo-andrographolide 2.3%)
doesn’t cause significant reduction of progesterone
concentration in pregnant rats and suggest that at
therapeutic dose, A. paniculata extract cannot induce
progesterone-mediated termination of pregnancy. Based on the
above studies it is obvious that A.paniculata may have
antifertility effect depending on the type and quality of
preparation used. It is therefore of important to properly
evaluate the male and female reproductive toxicity effects
of the A. paniculata extracted. The teratogenicity effect of
the herb so far hasn’t been evaluated and it is of our
interest to study the possible teratogenicity effect of the
similar extract.

Owing to the extensive knowledge of this
herb for treatment of various serious ailments, it is deemed
necessary to study in detail the broader benefits of this
herb to humans. Since it has been known that the biological
activities shown by the herb is mainly due to
andrographolide and it derivatives, it is vital to prolong
the shelf-life of these compounds. This is carried out by
determining standardised and consistent raw material with
optimum bioacive compound together with its metabolite
obtained, dry and store at optimum conditions to reduces the
rate of andrographolide degradation.

Malays believe this A. paniculata can
treat Diabetes mellitus. Diabetes mellitus is a group of
metabolic diseases characterized by hyperglycemia resulting
from defects in insulin secretion, insulin action, or both.
Several pathogenic processes are involved in the development
of diabetes. These range from autoimmune destruction of the
b -cells of the pancreas with consequent insulin deficiency,
to abnormalities that result in resistance to insulin
action. Often, impairment of insulin secretion and defects
in insulin action frequently coexist in the same patient,
and it is often unclear which abnormality, if either alone,
is the primary cause of the hyperglycemia. In Type 1
diabetes, there is total destruction of pancreatic b -cells
and patient is dependent on exogenous insulin. Type 2
diabetes is more prevalent, and the cause is a combination
of resistance to insulin action and an inadequate
compensatory insulin secretory response. As a result, a
poorly controlled Type 2 patient will require a lot more
insulin to lower the glucose level in the blood. The
mechanism is still not clearly identified.

There are many types of therapeutic
approach used to treat Type 2 diabetes. While sulfonylureas
stimulate b -cells to secrete more insulin and hence lower
blood glucose concentration, metformin therapy improves
insulin sensitivity. On the other, the newer antidiabetic
agents, the thiazolidinedione derivatives, have been shown
to cause increase glucose utilization in both muscle and
liver cells in vitro, and reduce insulin resistance by
modifying the glucose transporter (GLUT) system, especially
GLUT1 and GLUT4, in both muscles and liver.

A. paniculata has been in a number of
studies to exert antihyperglcaemic and hepatoprotective
effects (6,7). Aqueous extract of Andrographis paniculata
when administered orally (2 g/kg) did not lower the blood
glucose levels in fasted rats but significantly inhibit the
increase in blood glucose during oral glucose tolerance
test. Whereas, glibenclamide (10 mg/kg) reduced the blood
glucose levels in both experiments (Asmawi and Ahmad, 1987).
It is known that orall glucose tolerance test is a more
sensitive method to detect diabetes mellitus (Herfindal and
Hirschman, 1984) The not so active hypoglycaemic activity of
the extract was thought due to insufficient amount of the
active ingredient had been extracted from the plant. Thus,
it was decided to extract the plant with less polar solvent,
methanol and then to extract the methanol extract obtained
serially with chloroform, butanol and water. In doing so, we
hope that the active antidiabetic compound(s) would be
concentrated in one of the fractions. It was found that the
methanol extract, butanol and water fractions (1 gm/kg) did
not lower the blood glucose level in normoglycaemic rats nor
inhibit the increase in blood glucose level during glucose
tolerance test. However, the chloroform fraction of the
plant extract (1 g/kg) significantly reduced both the blood
glucose level of normoglycaemic rats and during glucose
tolerance test. These results suggested that the
antidiabetic component of the Andrographis paniculata were
present in the chloroform fraction of the extract that is
relatively less polar fractions as compared to the water and
butanol fractions (Ahmad and Asmawi, 1990). It can be
concluded that the conventional usage of Andrographis
paniculata in the form of an aqueous decoction is relatively
less effective as an antidiabetic agent. The best
antidiabetic activity from this plant can only be obtained
if the extract is prepared to include the active compound(s)
in the chloroform fraction. This can be prepared in the form
of standardised extract. Although by doing activity guided
isolation, the active antidiabetic compound(s) can be
isolated and identified, the compound isolated can not be
commercially developed into modern antidiabetic drug because
it would make it to costly to produce. Therefore, the
production of standardised Andrographis paniculata extract
as an antidiabetic drugs commercially more viable.

The increased use of herbal medicines has
resulted in increased concern about both the efficacy and
safety of these products. Indeed, there have been a number
of reports of toxic effects from traditional and herbal
medicines - the WHO database currently lists 8985 adverse
drug reaction reports in which herbal preparations are
suspected of being implicated. The increasing use of herbal
medicines means that there is a potential for more drug
interactions, particularly between the herbal products and
conventional ‘Western’ medicines where the former is often
used by individuals with chronic health conditions. There
have been a number of interactions reported to date where
the toxicity and interaction studies are mostly conducted on
herbal plants/products found in the developed countries. For
example, Echinacea could cause hepatotoxicity and therefore
should not be used with other known hepatotoxic drugs such
as anabolic steroids, amiodarone, methotrexate and
ketoconazole.

Literature survey indicated that there are
very few toxicity and herb-drug interaction studies done on
local medicinal plants. Few studies on herb-drug interaction
of local medicinal plants and herbal products have been
reported by the author and its group (Hussinet al, 1998;
Taher and Hussin, 1998; Hussin, Baie and Asmawi, 1999;
Hussin et al, 1999). Due to its promising and high
commercial potential, we have chosen Hempedu Bumi to further
develop their scientific uses through scientific herb-drug
interaction studies of the standardized extract of this
plant. It is our hope that through this project, we will be
able to formulate new pharmaceutically formulated product of
Hempedu Bumi which is efficacious and safe for consumer
consumption.

Development and Clinical Studies of
Hempedu Bumi (Andrographis paniculata) as a Commercial
Preparation for the Treatment of Diabetes

Project 2: Extraction, isolation, characterization and
analysis of the chemical constituents from Andrographis
paniculata for use as markers in the standardization of
extracts and manufacture of its commercial formulation
for clinic trial

VitalTea®Misai Kucing and King of Bitter (Hempedu Bumi)
This traditional herbal mixture is generally used to reduce
high blood pressure, diabetics and joint pain. It is also
use to boost immune system.